P
US8476235B2ActiveUtilityPatentIndex 60

Crystalline D-isoglutamyl-D-tryptophan and the mono ammonium salt of D-isoglutamyl-D-tryptophan

Assignee: TAM TIM FATPriority: Nov 28, 2006Filed: Feb 20, 2012Granted: Jul 2, 2013
Est. expiryNov 28, 2026(~0.4 yrs left)· nominal 20-yr term from priority
Inventors:TAM TIM FATN ZEMBA BLAISELEUNG-TOUNG REGISWANG YINGSHENGZHAO YANQINGYU LILY
A61P 37/06A61P 37/00A61P 17/06C07K 5/0215A61K 38/00A61K 38/05C07K 1/107C07K 1/30C07K 5/06
60
PatentIndex Score
1
Cited by
22
References
24
Claims

Abstract

A process for making pure crystalline D-isoglutamyl-D-tryptophan is provided which includes the step of deprotecting essentially pure N-tert-butoxycarbonyl-D-isoglutamyl-D-tryptophan or its diester to yield essentially pure D-isoglutamyl-D-tryptophan. A process is also provided for the preparation of pure mono ammonium salt of D-isoglutamyl-D-tryptophan from essentially pure N-tert-butoxycarbonyl-D-isoglutamyl-D-tryptophan. D-isoglutamyl-D-tryptophan, ammonium salt (1:1) is a stable pharmaceutical solid.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. Crystalline H-D-iGlu-D-Trp-OH, ammonium salt (1:1) characterized by the x-ray powder diffraction pattern as illustrated in  FIG. 2 . 
     
     
       2. Crystalline H-D-iGlu-D-Trp-OH, ammonium salt (1:1) characterized by the following X-ray powder diffraction pattern expressed in terms of inter-planar distances d, Bragg's angle 2 theta, and relative intensity (expressed as a percentage with respect to the most intense ray): 
       
         
           
                 
                 
                 
               
                     
                 
                   Angle [°2 theta] 
                   d-value [Å] 
                   Rel. Int [%] 
                 
                     
                 
                     
                 
                 
                 
                 
               
                   9.29 
                   9.517 
                   4.1 
                 
                   12.19 
                   7.258 
                   4.5 
                 
                   13.93 
                   6.354 
                   76.2 
                 
                   15.17 
                   5.837 
                   27.4 
                 
                   16.49 
                   5.371 
                   9.8 
                 
                   17.18 
                   5.157 
                   3 
                 
                   18.56 
                   4.778 
                   31.6 
                 
                   18.88 
                   4.696 
                   10.5 
                 
                   20.02 
                   4.431 
                   100 
                 
                   22.28 
                   3.986 
                   3 
                 
                   23.31 
                   3.814 
                   4.6 
                 
                   23.66 
                   3.757 
                   9.8 
                 
                   24.03 
                   3.7 
                   52.9 
                 
                   24.37 
                   3.649 
                   26.3 
                 
                   25.07 
                   3.549 
                   11.4 
                 
                   25.61 
                   3.475 
                   5.6 
                 
                   25.96 
                   3.43 
                   5 
                 
                   27.62 
                   3.227 
                   29.7 
                 
                   28.12 
                   3.17 
                   55.7 
                 
                   28.49 
                   3.131 
                   12.2 
                 
                   29.52 
                   3.023 
                   23.1 
                 
                   30.27 
                   2.951 
                   3.7 
                 
                   30.64 
                   2.915 
                   7.9 
                 
                   31.31 
                   2.854 
                   11.8 
                 
                   31.7 
                   2.821 
                   29.6 
                 
                   32.16 
                   2.781 
                   19.2 
                 
                   32.81 
                   2.728 
                   16 
                 
                   33.78 
                   2.652 
                   7.4 
                 
                   34.14 
                   2.625 
                   5.1 
                 
                   35.76 
                   2.509 
                   16 
                 
                   36.94 
                   2.431 
                   11.6 
                 
                   37.58 
                   2.391 
                   25.6 
                 
                   38.03 
                   2.364 
                   12.5 
                 
                   39.22 
                   2.295 
                   1.9. 
                 
                     
                 
             
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
       3. Crystalline H-D-iGlu-D-Trp-OH, ammonium salt (1:1) having an X-ray powder diffraction pattern comprising peaks at 2θ angles of approximately 13.93, 20.02, 24.03 and 28.12 degrees. 
     
     
       4. Crystalline H-D-iGlu-D-Trp-OH, ammonium salt (1:1) having an X-ray powder diffraction pattern comprising peaks at approximately 9.29, 12.19, 13.93, 15.17, 16.49, 17.18, 18.56, 18.88, 20.02, 22.28, 23.31, 23.66, 24.03, 24.37, 25.07, 25.61, 25.96, 27.62, 28.12, 28.49, 29,52, 30.27, 30.64, 31.31, 31.70, 32.16, 32.81, 33.78, 34.14, 35.76, 36.94, 37.58, 38.03 and 39.22 degrees 2θ. 
     
     
       5. The crystalline salt of  claim 3  having an X-ray powder diffraction pattern comprising peaks at 2θ angles of approximately 13.93, 15.17, 18.56, 20.02, 24.03, 24.37, 27.62, 28.12, 31.7 and 37.58 degrees. 
     
     
       6. Crystalline H-D-iGlu-D-Trp-OH, ammonium salt (1:1) characterized by the infrared absorption spectrum as illustrated in  FIG. 4 . 
     
     
       7. A pharmaceutical composition comprising the crystalline salt of  claim 1  and at least one pharmaceutically acceptable excipient. 
     
     
       8. A pharmaceutical composition comprising the crystalline salt of  claim 2  and at least one pharmaceutically acceptable excipient. 
     
     
       9. A pharmaceutical composition comprising the crystalline salt of  claim 3  and at least one pharmaceutically acceptable excipient. 
     
     
       10. A pharmaceutical composition comprising the crystalline salt of  claim 4  and at least one pharmaceutically acceptable excipient. 
     
     
       11. A pharmaceutical composition comprising the crystalline salt of  claim 5  and at least one pharmaceutically acceptable excipient. 
     
     
       12. A pharmaceutical composition comprising the crystalline salt of  claim 6  and at least one pharmaceutically acceptable excipient. 
     
     
       13. A method of treating psoriasis comprising administering an effective amount of the crystalline salt of  claim 1  or the pharmaceutical composition of  claim 7  to a subject in need thereof. 
     
     
       14. A method of treating psoriasis comprising administering an effective amount of the crystalline salt of  claim 2  or the pharmaceutical composition of  claim 8  to a subject in need thereof. 
     
     
       15. A method of treating psoriasis comprising administering an effective amount of the crystalline salt of  claim 3  or the pharmaceutical composition of  claim 9  to a subject in need thereof. 
     
     
       16. A method of treating psoriasis comprising administering an effective amount of the crystalline salt of  claim 4  or the pharmaceutical composition of  claim 10  to a subject in need thereof. 
     
     
       17. A method of treating psoriasis comprising administering an effective amount of the crystalline salt of  claim 5  or the pharmaceutical composition of  claim 11  to a subject in need thereof. 
     
     
       18. A method of treating psoriasis comprising administering an effective amount of the crystalline salt of  claim 6  or the pharmaceutical composition of  claim 12  to a subject in need thereof. 
     
     
       19. A method of selectively inhibiting proliferation of bone marrow cells in a subject in need thereof comprising administering an effective amount of the crystalline salt of  claim 1  or the pharmaceutical composition of  claim 7  to a subject in need thereof. 
     
     
       20. A method of selectively inhibiting proliferation of bone marrow cells in a subject in need thereof comprising administering an effective amount of the crystalline salt of  claim 2  or the pharmaceutical composition of  claim 8  to a subject in need thereof. 
     
     
       21. A method of selectively inhibiting proliferation of bone marrow cells in a subject in need thereof comprising administering an effective amount of the crystalline salt of  claim 3  or the pharmaceutical composition of  claim 8  to a subject in need thereof. 
     
     
       22. A method of selectively inhibiting proliferation of bone marrow cells in a subject in need thereof comprising administering an effective amount of the crystalline salt of  claim 4  or the pharmaceutical composition of  claim 10  to a subject in need thereof. 
     
     
       23. A method of selectively inhibiting proliferation of bone marrow cells in a subject in need thereof comprising administering an effective amount of the crystalline salt of  claim 5  or the pharmaceutical composition of  claim 11  to a subject in need thereof. 
     
     
       24. A method of selectively inhibiting proliferation of bone marrow cells in a subject in need thereof comprising administering an effective amount of the crystalline salt of  claim 6  or the pharmaceutical composition of  claim 12  to a subject in need thereof.

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